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NSAIDs Increase the Risk of Death

Should Anti-inflammatory Drugs be Prescription Only?

Feb 16, 2009 Stephen Allen Christensen

Merck's troubles with its signature drug, Vioxx, are only the tip of the iceberg. Mounting evidence reveals that all NSAIDs can aggravate heart disease.

Commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) like naproxen and ibuprofen may be harmful to people with cardiac disease. A new study shows that it isn’t just the cyclooxygenase 2 (COX-2) inhibitors (Vioxx, Celebrex, etc.) that cause heart problems. (Gislason G, Rasmussen J, Abildstrom S, et al. "Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure." Arch Intern Med. 2009;169:141-149)

The study, which included more than 107,000 people, showed dose-related increases in the risks of death and re-hospitalization for heart failure or heart attack with COX-2 inhibitors and other NSAIDs. While the selective COX-2 inhibitors seem to pose the highest risk to individuals with pre-existing heart problems, even over-the-counter NSAIDs can exacerbate heart disease.

Lead author Dr. Gunnar Gislason conceded that the study was observational—rather than a placebo-controlled trial—but he added, “…we have very consistent results…using two different statistical methods. And these results are similar to many other previous studies. I think the data are very convincing.”

The study’s authors expressed concern that the numbers of people who needed to be exposed to NSAIDs before a death occurred were quite low. In other words, a substantial number of people who can obtain these medications without a prescription should not be taking them, because the risk of death is significant.

How NSAIDs Work

NSAIDs exert their influence by interfering with the production of prostaglandins. Prostaglandins are a diverse group of chemicals that serve a multitude of physiologic functions:

Prostaglandins play a major contributory role in the inflammatory response. Reducing the levels of inflammatory prostaglandins helps to reduce pain and swelling; this is why NSAIDs are useful for people with arthritis.
Prostaglandins play a role in controlling the diameter of blood vessels in various organs and tissues of the body, such as the kidneys, heart, brain, and placenta. Reducing the levels of prostaglandins in these tissues can cause inappropriate constriction or dilation of veins and arteries.
Prostaglandins are involved in helping blood to clot in response to injury; limiting their production or activity may increase the risk of bleeding.
Prostaglandins help to protect the stomach lining from gastric acid. Without this protection, ulcers can form. Gastrointestinal ulceration is a side effect of NSAIDs.

Why Non-steroidal Drugs Cause Heart Problems

By reducing the levels of prostaglandins in the body, NSAIDs can increase blood pressure, promote sodium and water retention, and impair blood flow in already compromised vessels. These and other physiologic changes may aggravate pre-existing congestive heart failure, hypertension, or coronary artery disease.

Study Findings and Recommendations

All NSAIDs were associated with an increased risk for death, and this risk increased with the dose of NSAID
The increase in risk of death was highest with rofecoxib (Vioxx), celecoxib (Celebrex), and diclofenac (Voltaren)
Low doses of ibuprofen and naproxen were not associated with an increased risk of death, but the risk for hospitalization because of heart attack was highest in patients who received naproxen (Aleve, Naprosyn, Anaprox)
Any NSAID use increased the risk for both congestive heart failure and heart attack

Based on evidence of NSAID-induced injury to individuals with heart disease, in 2007 the American Heart Association suggested that such patients should take acetaminophen or aspirin as the initial treatment for musculoskeletal pain (including arthritis). Non-acetylated salicylates (salsalate, choline magnesium trisalicylate, and magnesium salicylate) are next in line; only when these treatments fail should NSAIDs be considered, and COX-2 inhibitors should be avoided whenever possible.

NSAIDs are part of the pharmaceutical landscape; some are available without prescription. The safety of ANY medication should be considered before it becomes part of a person’s daily routine.

The copyright of the article NSAIDs Increase the Risk of Death in General Medicine is owned by Stephen Allen Christensen. Permission to republish NSAIDs Increase the Risk of Death in print or online must be granted by the author in writing.

NSAIDs and Heart Disease